Background: 

The anti-cancer drugs cisplatin (CDDP) and auranofin increase intracellular calcium concentration ([Ca²⁺]_i) in breast cancer (MCF-7) cells, while the elevated [Ca²⁺]_i induces apoptosis. Here we investigate drug induced [Ca²⁺]_i increase and the mechanisms by which they change Ca²⁺ transport.

Methods: 

Changes in the [Ca²⁺]_i were recorded using florescence microscopy and calcium-sensitive fluorescent dyes (i.e. fluo-4-AM). CDDP (0.001 - 10 mM), auranofin (1mM) and [Ca²⁺]_i modulators (caffeine; 10mM, nimodipine; 10mM, ionomycin; 10mM, thapsigargin; 500nM, and 2-APB; 50mM) were administered to cultured MCF-7 cells via a bath perfusion system.

Results: 

CDDP induced a concentration-dependent increase of [Ca²⁺]_i. Pre-application of the calcium channel blocker, nimodipine reduced this elevation significantly (46.6% increase; n=26) as well as the IP₃ receptor blocker 2-APB (71.4% increase; n=52). Surprisingly, when [Ca²⁺]_i was elevated due to a pre-application of caffeine, ionomycin or thapsigargin the subsequent application of CDDP was also significantly reduced compared to control (n=15; 37.8%, n=32; 34.9%, n=21; 53.7% increase respectively). Similarly, auranofin induced an increase in [Ca²⁺]_i in the MCF-7 cell-line.

Conclusion: 

CDDP and auranofin both elevate [Ca²⁺]_i by Ca²⁺ entry and Ca²⁺ release from the stores. A pre-elevation of [Ca²⁺]_i by releasing Ca²⁺ from the stores reduces this elevation significantly. The exact mechanisms remain unclear. Further investigations are required to determine pathways that are regulated by CDDP and auranofin and are involved in the elevation of [Ca²⁺]_i.